The importance of improving the treatment of cancerous tissue needs scarcely to be emphasized. Local cancerous tissue is typically treated with surgery and/or radiation therapy. Radiation therapy has been an important part of cancer treatment ever since malignant tumors were discovered to be susceptible to ionizing radiation.
A fundamental principal of radiation therapy is to deliver a therapeutic dose to the target tissue while minimizing the dose to surrounding healthy tissue, i.e., maximizing the therapeutic ratio. This is particularly challenging for deeply seated cancers since external therapy beams must traverse relatively large volumes of healthy tissue in order to reach the target. A variety of techniques have been developed to improve the therapeutic ratio for such external beam treatments, including three-dimensional (3-D) treatment planning, use of non-coplanar beams, stereotactic radiosurgery, intensity modulation, and charged particle therapy (e.g., protons). Radiation must be of a very high energy (short wavelength) in order to treat cancers that are deeply seated inside the body because this radiation must pass through overlying skin and sometimes other tissue, such as bone, which is more x-ray absorbent. Because such therapeutic radiation can be harmful to healthy tissue, the use of these techniques is limited to the dose amount that can be tolerated by the healthy tissues surrounding the target cancer.
Intraoperative radiation and brachytherapy are techniques developed to reduce the impact of radiation therapy to surrounding healthy tissues. During intraoperative therapy, adjacent healthy tissues are physically moved such that a radiation applicator can be applied directly to the target volume while applying a reduced amount of radiation to the adjacent healthy tissues. The radiation applicator can be an external photon beam generator, electron generator, or a radioactive material.
Brachytherapy involves implanting radioactive sources near or within cancerous tissue to provide interior radiation while minimizing exposure to surrounding healthy tissue. Brachytherapy has proven useful, but still carries the inherent risk of a radiation source that cannot be turned off. The handling, preparation, and use of such sources require that physicians, physicists, radiologists, and other personnel experience occupational exposure to ionizing radiation. Radioactive sources must be stored in shielded storage areas. Further, there are environmental and security issues regarding the disposal of these radioactive sources.
A number of devices have been developed for applying soft x-rays to interior cancer tissues in attempts to reduce radiation deposition in surrounding normal tissues. Some such devices generate soft x-rays inside the body using small x-ray generators inserted near or into cancer tissue. For example U.S. Pat. No. 5,153,900 to Nomikos et al. and U.S. Pat. No. 5,442,678 to Dinsmore et al. disclose a device consisting of a miniaturized low power x-ray source that generates electrons from an extracorporeal cathode, which emits these electrons down an evacuated tube towards an anode that is positioned inside the body. The x-ray radiation is then generated as these electrons impact the anode and is emitted approximately spherically. U.S. Pat. No. 5,369,679 to Sliski et al. and U.S. Pat. No. 5,422,926 Smith et al. disclose improvements to the x-ray generator. U.S. Pat. No. 5,452,720 to Smith et al. and U.S. Pat. No. 5,528,652 to Smith et al. disclose a method of using such a device that generates x-rays from an electron beam inside the body for the purpose of treating brain tumors.
A balloon shaped applicator system to attach to the end of the electron transmitting tube has been disclosed in U.S. Pat. No. 5,566,221 to Smith et al. and U.S. Pat. No. 5,621,780 to Smith et al. In this applicator system, a variable sized balloon is used to position the anode in the center of a body cavity, such as the bladder, to ensure a uniform dose is delivered to the entire inner surface of the cavity. An additional applicator system design is disclosed in U.S. Pat. Nos. 6,285,735, 6,301,328, and 6,421,416, each to Sliski et al. The additional applicator system expands upon the balloon applicator system to include cylindrical dose distributions and flat dose distributions through a surface external to the electron transmitting tube's anode. A biocompatible sheath for such an electron transmitting tube is disclosed in U.S. Pat. Nos. 6,245,047 and 6,480,567, each to Feta et al. The biocompatible sheath is composed of a polymer sheath that slips over the tube and creates a barrier between the body and the device. This allows the device to be reused in multiple patients by simply replacing the biocompatible sheath. These above devices have the difficulty that if the electron beam impacts the tube wall, then Bremsstrahlung radiation is emitted laterally into normal tissue. Another problem with placing an anode inside the body is that the anode will generate heat since only a small fraction of the energy from the electrons is converted to x-ray energy.
U.S. Pat. No. 5,737,384 to Fenn discloses a tube for insertion into the body similar to that described above in which electrons are transmitted from an extracorporeal cathode to an anode at the distal end of a tube inside the body. This device combines multiple tubes for the purpose of combining microwave energy with x-ray energy in the treatment volume. Radiofrequency treatment combined with x-ray or laser treatment is also suggested. However, this device does require that a large voltage be created inside the body in order to accelerate the electrons. There will also be significant heat generated at the anode when the x-rays are created at therapeutic intensities.
U.S. Pat. No. 5,428,658 to Oettinger et al. discloses a themionic x-ray source mounted at the end of a flexible probe for insertion inside the body. This radiation device uses a laser beam to cause the emission of electrons at the device tip, where they are then accelerated over only a short distance before impacting an anode to produce x-ray radiation. Subsequent improvements to the thermionic flexible x-ray source are disclosed in U.S. Pat. Nos. 6,195,411, 6,320,932, 6,493,419, 6,480,568, and 6,480,573, each to Dinsmore. These devices require that a large voltage be created inside the body in order to accelerate the electrons after they have been stimulated at the cathode. There will also be significant heat generated at the anode when the x-rays are created at therapeutic intensities.
U.S. Pat. No. 5,090,043 to Parker et al. and U.S. Pat. Reexam No. 34,421 to Parker et al. disclose a miniature x-ray device for insertion inside the body with a glass enclosure. The device includes inserting a cathode and anode in a vacuum housing inside the body. U.S. Pat. Nos. 5,854,822, 6,069,938, 6,095,966, 6,108,402, 6,095,966, 6,289,079, 6,377,846, 6,415,016, 6,473,491, 6,477,235, and 6,546,077, each to Chornenky et al., disclose a similar miniature x-ray device for insertion inside the body and subsequent improvements to such a device. The miniature x-ray generator of the Chornenky Patents is powered by the insertion of a coaxial cable into the body to provide a potential for accelerating electrons from the cathode to the anode. Diamond is suggested for use in the anode and the housing. The device is suggested for use in treatment of Barrett's esophagus and in restenosis. This device still requires that a large voltage be created inside the body in order to accelerate the electrons. There is also significant heat generated at the anode when the x-rays are created at therapeutic intensities.
U.S. Pat. No. 6,275,566 to Smith et al. discloses a miniature x-ray device similar to those of the Chornenky Patents in which the entire x-ray generator, including the cathode and anode, are placed inside a miniature vacuum tube. The device is driven using an external voltage source similar to the miniature x-ray device disclosed in the Chornenky Patents, but it uses an alternating current rather than a direct current. The alternating current causes the anode and cathode to alternate with the same frequency as the current. With x-rays being generated at both electrodes, it is easier to cool each particular electrode because each electrode runs cooler than if either was the only point at which x-rays were generated. This device still requires that a large voltage be created inside the body in order to accelerate the electrons after they have been stimulated at the cathode. There is also significant heat generated at the anode when the x-rays are created at therapeutic intensities.
U.S. Pat. No. 6,001,054 to Regulla et al. discloses a device for increasing the local dose of ionizing radiation by introducing a metal surface near a tumor for the purpose of increasing local backscatter. The metal surface would be near the tumor and have a shape roughly conforming to the tumor. Ionizing radiation would be introduced from outside the body using standard external beam techniques. At the site of the tumor, the implanted metal surface creates backscatter radiation in the area of the tumor that increases local dose rates near the tumor between 2–200 times. The disclosure states that radiation from 40–400 keV will see the greatest increases in local dose rates, and suggests using metal surfaces with atomic numbers of approximately 20–40. The device is an improvement over standard external beam therapies, but still deposits a significant amount of radiation between the skin where the external beam enters the body and the tumor. Due to the fact that radiation between 40–400 keV is highly absorbed, significant irradiation of normal tissue between the skin and the tumor is expected.
U.S. Pat. No. 5,816,999 to Bischoff et al. discloses a device that delivers soft x-rays to target cancers via a flexible radiation transmitting catheter. This device transmits the soft x-rays generated outside the body directly to the site of an interior cancer. The soft x-rays are transmitted along a curved path through flexible hollow glass fibers by means of multiple surface specular reflections. Such a system involves a substantial reduction in beam intensity due to the multiple reflections required to transmit x-rays through a curved path and due also to the small transmission area of the capillaries relative to the total cross-sectional area of the radiation needle. The critical angle for total external reflection decreases as the energy of the x-ray photons increases. Consequently, a flexible x-ray transmitting radiation needle is limited to ultra soft x-rays with a cancer penetration depth on the order of millimeters and furthermore the large loss in radiation intensity caused by the reflections may increase the exposure time beyond clinically acceptable limits. This device may be useful for the treatment of surface lesions, but is not very useful for the treatment of larger neoplasms.
U.S. Pat. No. 5,816,999 to Bischoff et al. also discloses a dispersive distal cap. The cap absorbs parallel radiation from the flexible hollow glass fibers, and transmits it in a shaped pattern using fluorescence. The distal dispersive cap requires that primary x-rays and secondary, fluorescent x-rays must both be transmitted through the distal dispersive cap. This can lead to massive absorption losses, especially for the low energy (less than 20 keV) radiation transmitted by curved flexible hollow glass fibers using multiple specular reflections.
In view of the known devices for treating interior cancers, it is desirable to have an improved device for targeting interior cancerous tissues with ionizing radiation from an extracorporeal source. It is also desirable to have a radiation therapy device that minimizes the exposure of surrounding normal tissue to radiation. Further, it is desired to provide a radiation therapy device that applies a minimal amount of heat and voltage to the body during radiation therapy. A device that can deliver therapeutic radiation precisely to targeted tissues could have significant uses in a wide variety of therapeutic radiation oncology applications.